Physicians' Academy for Cardiovascular Education

Amylin analogue reduces body weight in individuals with overweight and obesity

One-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose finding phase 2 trial

Literature - Lau DCW, Erichsen L, Francisco AM et al., - The Lancet 2021, S0140-6736(21)01751-7. doi: 10.1016/S0140-6736(21)01751-7

Introduction and methods


There are only few approved pharmacotherapies for weight management in individuals with overweight or obesity, and weight loss with these agents ranges from 3-9% relative to placebo at 1 year [1,2]. The STEP trial program showed that the GLP-1 receptor agonist semaglutide resulted in significant weight loss [3-5], but there is room for novel agents given the heterogeneity of obesity and the differential response to treatments.

Amylin is hormone produced in the β cells of the pancreas and secreted together with insulin in response to food intake. It creates a satiety signal, resulting in slowing gastric emptying and suppressing the post-prandial glucagon response. Cagrilintide is a long-acting, acylated amylin analogue and has shown to reduce food intake and bodyweight [6-8].

This study examined the effect of ascending doses of cagrilintide on bodyweight, safety and tolerability in participants with overweight or obesity. Also, changes in waist circumference and cardiometabolic parameters with cagrilintide were compared with placebo and the GLP-1RA liraglutide.

Study design

A multicenter, randomized, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial was conducted. The trial had a 26-week treatment period, including a dose-escalation period of up to 6 weeks, and a 6-week follow-up without treatment. Adult of non-childbearing potential with a BMI of ≥30 kg/m2, or ≥27 kg/m2 with hypertension or dyslipidemia were eligible. Individuals with diabetes were excluded. 706 Participants were randomized to subcutaneous injections of one-weekly cagrilintide (0.3, 0.6, 1.2, 2.4, or 4.5 mg), once-weekly liraglutide or volume-matched placebo. All participants were counselled on diet and physical activity.


Primary endpoint was the percentage change in bodyweight from baseline to week 26.

Main results


Use of the amylin analogue cagrilintide in doses ranging from 0.3-4.5 mg for 26 weeks in addition to lifestyle interventions resulted in dose-dependent weight loss in adults with overweight or obesity. It was well tolerated. The authors write: ‘Cagrilintide presents an opportunity to expand the range of existing pharmacotherapies for weight management. Moreover, cagrilintide could be explored in combination with other agents for a potential additive weight-loss effect.’


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Find this article online at The Lancet

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